Lysophosphatidylcholine (LPC) transferred from oxidatively modified low density lipoprotein (Ox-LDL) to the endothelial surface membrane has been shown to produce a selective unresponsiveness to cell surface receptor-regulated endothelium-dependent relaxation (EDR) in the rabbit aorta and porcine coronary artery. To determine its mechanism, the effects of LPC or Ox-LDL on intracellular signals in endothelial cells were examined. The results from this experiment indicate that LPC inhibits the early transmembrane signaling pathway in endothelial cells, and Protein Kinase C (PKC) activation could at least partially be involved in the negative regulation by LPC. These intracellular actions of LPC may play a role in the mechanism of the LPC-induced impairment of EDR in response to cell surface receptor-mediated stimulations.To determine whether Ox-LDL modulates endothelial fibrinolytic system, levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) a
… Morentigens in the conditioned medium were measured by ELISA. The results indicate that Ox-LDL stimulates PAI-1 release by the transferable hydrophilic lipid(s) in Ox-LDL, especially LPC, while Ox-LDL inhibits t-PA release by 25-hydroxycholesterol and 7-ketocholesterol or other transferable lipid(s) from Ox-LDL to albumin rather than LPC. Thus, lipid products in Ox-LDL may impair endothelial fibrinolysis. We further examined the effects of Ox-LDL on the secretion of endothelin-1-like immunoreactivity (ET-1-LI) by the cultured vascular endothelial cells (porcine aortic endothelial cells and human umbilical vein endothelial cells), considering the possible relevance of ET-1 to the atherosclerosis and hypercholesterolemia. The results show that LPC in Ox-LDL causes suppression of ET-1-LI release, which may counteract the vasoconstricitve properties of atherosclerotic arteries. Furthermore, LPC in Ox-LDL causes the increase of the endothelial adhesiveness to polymorphonuclear leukocytes (PMNs), which augments PMNs-induced impairment of EDR in porcine coronary artery. This is due to increased expression of intercellular adhesion molecule-1 in endothelium of the porcine coronary artery, and the activation of PKC by LPC in Ox-LDL may at least in part be involved in these mechanisms. Less